Predictors of marginal ulcers after laparoscopic Roux-en-Y gastric bypass

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Predictors of marginal ulcers after laparoscopic Roux-en-Y gastric bypass Neil H. Bhayani, MD, MHS,* Tolulope A. Oyetunji, MD, MPH, David C. Chang, MPH, MBA, PhD, Edward E. Cornwell, III MD, Gezzer Ortega, MD, and Terrence M. Fullum, MD Department of Surgery, Howard University College of Medicine, Washington, District of Columbia

article info

abstract

Article history:

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a highly effective therapy for

Received 9 March 2012

morbid obesity. As the most common postoperative complication, marginal ulcers (MU)

Received in revised form

present a significant disease burden. The etiology of marginal ulcers after gastric bypass has

23 April 2012

not been clearly defined. The purpose of this study was to identify independent risk factors

Accepted 1 June 2012

for MU.

Available online 19 June 2012

Methods: We performed a retrospective study of a single surgeon’s experience performing LRYGB between July 2001 and January 2006 in a United States private practice and university

Keywords:

hospital. We investigated patient factors and comorbidities associated with the development

Gastric bypass

of marginal ulcers. The five most common comorbidities were hypertension, type 2 diabetes

Marginal ulcer

mellitus, gastroesophageal reflux disease, hyperlipidemia, and obstructive sleep apnea. We

Predictors

analyzed these factors using multivariate logistic regression adjusting for demographics,

Comorbidities

BMI, and all comorbidities.

Anastomotic ulcer

Results: In our 763 patients, 89% were female, 84.7% were African-American, and the mean BMI was 50.2 kg/m2 before surgery. Marginal ulcers occurred in 23 patients (3.01%) over a mean of 64 months. On c2 analysis, hypertension, gastroesophageal reflux disease, hyperlipidemia, and sleep apnea were significantly correlated with MU. On multivariate analysis, the odds of marginal ulcer formation were 7.84 among hypertensive patients with a 95% confidence interval of 1.75e35.06 (P ¼ 0.007). Hypertension was the only significant predictor of marginal ulcer disease. Conclusion: In our study, marginal ulcers occurred more frequently in patients with preoperative hypertension. At higher risk, these patients could be good candidates for extended acid suppression prophylaxis after LRYGB. ª 2012 Elsevier Inc. All rights reserved.

1.

Introduction

Marginal ulcers (MU) develop after laparoscopic Roux-en-Y gastric bypass (LRYGB) as a common complication. The creation of a gastrojejunostomy is prone to ulcer formation,

occurring predominantly on the jejunal side. Traditional rates of marginal ulceration were as high as 16%, but more recent series suggest a lower rate of marginal ulceration from 1%e9% [1e4]. A variety of acid suppression regimens, prophylactic and therapeutic, are employed in decreasing the rate of MU.

* Corresponding author. Department of Surgery, Howard University Hospital, 2041 Georgia Ave, NW Suite 4B04, Washington, DC, USA. Tel.: þ1 202 865 1441. E-mail address: [email protected] (N.H. Bhayani). 0022-4804/$ e see front matter ª 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2012.06.003

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These treatments are not targeted because the patient and procedural factors that contribute to the development of MU are not well defined. Previous retrospective studies have shown limited and sometimes conflicting results. Patient variables such as age, gender, or BMI do not confer a higher risk [5]. Some baseline comorbidities, such as diabetes mellitus, coronary artery disease, peptic ulcer disease, NSAID use, or tobacco use, do not show significant correlation with marginal ulcers [6]. In conflicting studies, others have demonstrated a correlation between NSAID, steroid, and tobacco use and an elevated risk of perforated marginal ulcer [7e9]. There is substantial overlap between risk factors that contribute to peptic ulcer disease, gastroesophageal reflux disease (GERD), and MU, but the role of Helicobacter pylori remains unclear [10]. Operative considerations should include the use of absorbable suture for the gastrojejunostomy and creation of a smaller (<50 mL) gastric pouch to decrease MU risk [8,11]. Acute or chronic inflammation from complications such as staple line dehiscence increases an individual’s risk for MU [8]. In the absence of a clear pathogenesis, acid suppression regimens have been employed empirically. Prophylaxis in the perioperative period is extremely variable without strong evidence to recommend the optimal type or duration, or for which patients prophylaxis is most beneficial. In this retrospective analysis of our patients, we hope to identify risk factors for MU. These risk factors may be used to select patients for postoperative prophylaxis.

2.

Methods

This study consisted of all patients who underwent LRYGB performed by a single surgeon between July 2001 and January 2006. Our database was created in 2004. All data before 2004 were collected retrospectively and all data thereafter were collected prospectively on preapproved, standardized datasheets. The surgeon performed all surgeries with the assistance of a general surgery resident or a minimally invasive surgery fellow in both university and private hospital settings. Patients were drawn from urban and suburban settings in the greater BaltimoreeWashington area. The study was approved by the institutional review board. The primary outcome was the diagnosis of a marginal ulcer. Demographic covariates were height, preoperative weight (after attempts at managed medical weight loss), BMI, gender, and self-reported race. Older patients were defined as 50 y of age. Preoperative comorbidities were recorded after preoperative evaluation based on 1) self-reporting, 2) patient medication lists, and 3) new diagnoses discovered during preoperative evaluation. Patient comorbidities were verified at the final preoperative assessment. The five most prevalent comorbidities were selected for analysis: hypertension (HTN), hyperlipidemia, type 2 diabetes mellitus (DM), GERD, and obstructive sleep apnea. We employed a consistent and systematic preoperative program for the evaluation and treatment of ulcer diathesis and known risk factors. Patient interviews included specific questions for symptoms of dyspepsia or peptic ulcer disease.

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All patients underwent a preoperative esophagogastroduodenoscopy. Preoperative history and findings on endoscopy determined the need for brushings or biopsies for H. pylori. All patients pathologically diagnosed with H. pylori infection were treated with proton pump inhibitors and two first-line antibiotics determined by patient allergies and insurance formularies. The operative procedure remained uniform during this time period. Both the gastrojejunostomy and the jejunojejunostomy were created using a linear stapler. A single row of continuous 2-0 silk suture was used to close each enterotomy. Endoscopy was not performed at the time of surgery. Our approach to prophylaxis for and treatment of marginal ulcers focused on routine acid suppression and mucosal protection. Postoperatively, patients with a history of GERD or preoperative symptoms of dyspepsia were maintained on their preoperative acid suppression regimens. All other patients received 60 d of over-the-counter famotidine or omeprazole. Patients who developed symptoms of MU were placed on esomeprazole (40 mg daily) and carafate and had upper endoscopy performed by the surgeon. Any endoscopically visualized ulcer, acute or chronic, on the jejunal side of the gastrojejunostomy was diagnosed as MU. If MU was seen on endoscopy, full-dose esomeprazole was continued for 1 y. If MU was not seen on endoscopy and biopsies of the gastric pouch were negative for H. pylori, 6e8 wk of esomeprazole were prescribed. In both groups, repeat upper GI endoscopy was performed in 6e8 wk. All statistical analysis was performed using Stata SE version 12 (College Park, Texas). The t-test was used for continuous variables including BMI. c2 analysis compared the discrete variables for bivariate measures. Logistic regression of comorbidities was used in the multivariate analysis to identify risk factors by association.

3.

Results

The variables and outcome of marginal ulceration were analyzed in 763 consecutive patients recorded between July 2001 and January 2006. The study sample, described in Table 1, was a predominantly African-American (84.7%) group of

Table 1 e Study sample descriptors. n (%) Demographics Total Black Elderly (age 50) Female Comorbidities Mean BMI, kg/m2 HTN Type 2 DM GERD Hyperlipidemia Arthritis Sleep apnea Marginal ulcers

763 646 (84.7) 182 (23.9) 679 (89.0) 50.2 438 (57.4) 185 (24.5) 205 (26.9) 233 (30.5) 327 (42.9) 141 (18.5) 23 (3.01)

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female subjects (89%), most of whom were below the age of 50 (76.1%). Patients had a mean preoperative BMI of 50.2, ranging from 35 to 83, and had at least one comorbidity. There were 23 patients who were diagnosed with marginal ulcers, for a cumulative incidence of 3.01%. This incidence was calculated for a mean of 63.9 mo of follow-up as of January 2009. On c2 analysis, the demographics of patients with and without marginal ulcers were not significantly different, as shown in Table 2. In the group that developed marginal ulcers, GERD (47.8%) and hyperlipidemia (52.2%) were more prevalent than in the non-MU group (26.2% and 29.9%, respectively). Arthritis and type 2 diabetes were not significantly different in prevalence between the two groups. Hypertension was significantly more prevalent in the MU than in the non-MU group (91.3% versus 56.4%). Among patients with marginal ulcers, 39.1% had obstructive sleep apnea, which was significantly greater than the 17.8% of patients without marginal ulcers. On multivariate analysis, the association between demographics and marginal ulcer formation was not significant (Table 3). While significantly associated with marginal ulcers on bivariate analysis, obstructive sleep apnea, hyperlipidemia, and GERD did not have the same correlation on multivariate analysis. Patients with preoperative hypertension were 7.84 times more likely to develop marginal ulcers. The 95% confidence interval for the odds ratio ranged from 1.75 to 35.06, with a P ¼ 0.007. On multivariate regression analysis, hypertension was the only risk factor significantly associated with marginal ulcers.

4.

Discussion

Marginal ulcer is the most common complication after LRYGB. Despite routine prophylactic acid suppression, our study revealed a 3.01% incidence of marginal ulcers, consistent with current literature. The only significant difference between our population and those previously reported was the higher proportion and absolute number of African-American patients. As the pathogenesis of MU among Black and nonBlack patients is likely to be similar, we believe our conclusions to be readily generalizable to the bariatric population at

Table 2 e Bivariate analysis of risk factors for marginal ulceration. Risk factor

No ulcer (n ¼ 740)

Marginal ulcer (n ¼ 23)

Demographics Black Elderly (age 50) Female Mean BMI, kg/m2 Comorbidities HTN Type 2 DM GERD Hyperlipidemia Arthritis Sleep apnea

n (%) 635 (85.8) 184 (24.1) 682 (89.4) 50.3

n (%) 11 (47.8) 5 (21.7) 18 (78.3) 50.3

0.35 0.8 0.09 0.48

417 177 194 221 316 132

21 8 11 12 11 9

0.001* 0.23 0.02* 0.02* 0.63 0.01*

(56.4) (23.9) (26.2) (29.9) (42.7) (17.8)

* Statistically significant for P < 0.05.

(91.3) (34.8) (47.8) (52.2) (47.8) (39.1)

P value

Table 3 e Multivariate analysis of risk factors for marginal ulceration. Risk factor Black Elderly Female Comorbidities HTN Type 2 DM GERD Hyperlipidemia Arthritis Sleep apnea

Odds ratio

95% confidence interval

P value

0.81 0.35 0.77

0.22e2.96 0.11e1.15 0.25e2.38

0.75 0.084 0.65

7.84* 0.91 2.17 2.42 1.17 2.32

1.75e35.06 0.33e2.47 0.89e5.31 0.97e6.03 0.47e2.90 0.89e6.02

0.007 0.85 0.09 0.057 0.73 0.085

* Statistically significant for P < 0.05.

large. Higher preoperative rates of HTN, GERD, hyperlipidemia, and sleep apnea were seen in the group that subsequently developed MU; however, on multivariate analysis only HTN remained statistically significant. Other comorbidities may not have maintained significance in multivariate analysis as a result of the smaller sample of patients with those diseases compared to HTN. Though hyperlipidemia showed a strong correlation and trend towards significance on multivariate analysis, the relatively small number of patients with hyperlipidemia resulted in a 53% power to detect a difference with a P < 0.05. With such a strong correlation between HTN and MU and strong statistical significance, this is unlikely to be spurious. Our study may reflect a less well-studied risk factor for MU disease: vascular disease. One potential etiology of marginal ulcer formation could be ischemia due to mesenteric vascular disease. Becker et al. [12], Cherry et al. [13], and Patel et al. [14] have reported gastric and duodenal ulcer disease refractory to traditional therapy that responded to mesenteric revascularization. While normally subclinical, mild mesenteric vascular disease may make unprotected small bowel more susceptible to the additional stress of acid exposure. Ulcers in animal studies have been associated with dysfunction of vascular endothelial cells [15]. Microvascular disease in our patients could compound the effect of an impaired mucosal barrier. While no such studies currently exist, data showing lower rates of marginal ulcers in patients whose hyperlipidemia and hypertension resolve after LRYGB may additionally strengthen this hypothesis. To our knowledge, our study is the first to show a strong association between HTN and MU. Rasmussen [5] did not find any significant increase in MU among hypertensive patients. Though the overall prevalence of HTN in that study was comparable to ours, the difference in results may arise from our larger sample size and mean follow-up of more than 5 y. The series by Sacks et al. [6] had comparable size; however, those investigators did not present information on preoperative hypertension. The retrospective design of this study imparts certain limitations. Information bias from imperfect data extraction or missing chart/database entries may lead to false conclusions. Preoperative comorbidities may have been misclassified due to patient underreporting, though preoperative workup and correlation with other subspecialists should have minimized the potential for this error. Further, patients with hypertension

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may be more likely to be treated with prophylactic aspirin for concomitant cardiovascular disease. These data are not available in our database and could be a potential confounder as NSAID use has been linked to MU. The creation of the database in 2004 may have increased surveillance for complications, resulting in systematic bias. Despite these caveats, we believe our data demonstrate a group of patients at high risk for MU. Prophylaxis in this population could substantially reduce morbidity, hospitalization for complications, and endoscopic interventions for the diagnosis or treatment of MU. While our postoperative prophylaxis included both histamine 2 receptor antagonists and proton pump inhibitors (PPIs), based on patients’ preference, tolerance, or previous use, PPIs were prescribed for all confirmed MUs. As such, we would recommend the use of PPIs as prophylaxis for patients with hypertension at high risk for marginal ulcer disease.

5.

Conclusions

In the bariatric population with hypertension, out data suggest a greater risk of marginal ulcers after LRYGB. Hyperlipidemia and sleep apnea may be contributors but did not achieve statistical significance in our study. Further evaluation of the relationship between hypertension and marginal ulcer disease is needed to help elucidate its pathophysiology. Based on our results, consideration for extended MU prophylaxis should be given to patients with preoperative hypertension.

Acknowledgment The authors thank Oluwaseyi Bolorundoro for statistical assistance.

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